Transdermal drug patch with attached pocket for controlled heating device

ABSTRACT

The present invention relates to a transdermal drug delivery system comprising a dermal drug delivery patch and a heating element compartment securable to the dermal drug delivery patch. A freely transferrable heating element is securable within the heating element compartment. A drug can be administered transdermally using the present invention by placing the dermal drug delivery patch upon a patient&#39;s skin at an administration site. A heating element compartment is secured to the dermal drug delivery patch and a freely transferrable heating element is placed within the heating element compartment. The heating element provides controlled heat to the dermal drug patch and the patient&#39;s skin and thereby improves dermal drug administration.

BACKGROUND

[0001] 1. The Field of the Invention

[0002] The present invention is directed toward a method and apparatusfor applying heat to a transdermal drug delivery system. Morespecifically, the invention is a securable compartment with acorresponding freely transferrable heating element for use with dermaldrug delivery patches.

[0003] 2. The Background Art

[0004] It has been discovered recently that the transdermal delivery ofcertain drugs can be facilitated by the application of heat. Controlledheat is provided to transdermal drug delivery patches using varioustechniques and apparatus such as heat generating patches. The heatgenerating patches sometimes utilize heat generated from chemicalreactions, such as an oxidation reaction, or may utilize heat generatedby an electrical current or some other method. One of the disadvantagesof prior art heating apparatus for the transdermal drug patches is thatthe heating element must be secured to the transdermal patch withoutcompromising the transdermal drug patch's attachment to the user's skin.In other words, sometimes when a user attempts to attach, replace, oradjust a heating patch or similar device, the drug delivery patch canbecome dislodged or otherwise made less secure. If the drug patch is notproperly situated, the drug delivery system may be compromised. It isimportant in transdermal drug delivery that the skin be in contact withthe formulation of the drug delivery patch to achieve efficient drugtransfer.

[0005] Several methods for attaching or integrating a controlled heatingelement have been taught in the prior art. For example, wraps,adhesives, and tapes have all been suggested as potential ways forattaching a heating element to a patient's body or to a transdermal drugpatch. Attempting to attach a heating element to a transdermal drugpatch these ways has several disadvantages.

[0006] When a prior art adhesive technique is used to apply the heatingelement to the drug patch, the process of applying the heating elementto the patch may cause the drug delivery patch to become less secure. Toapply the heating element using adhesive, the areas of the heatingelement that contain the adhesive must be pressed firmly against theheating patch to secure the heating element to the patch. During thisprocess, the drug delivery system may be unintentionally compromised.

[0007] In the event that the user needs to remove, replace or change theheating element, any attempts to remove the heating element may causethe adhesive of the transdermal patch to be compromised, and thus tocompromise the drug delivery. The continued removal and replacement ofthe heating element may cause the transdermal drug patch to lose enoughadhesive that the drug patch does not properly contact the skin andthereby become less effective and less secure.

[0008] A significant problem with using prior art wraps to secure aheating element to a transdermal drug patch is the potential for theheating element and/or the drug patch to become dislodged. If theheating element is secured using a wrap or tie, as the heating elementis being tied to or wrapped into the user or the drug patch on the user,the process of tying or wrapping the heating element can cause the drugpatch to lose contact with the skin of the patient and therebycompromise the drug delivery.

[0009] Another disadvantage of prior art teachings is the inconvenienceassociated with trying to remove a heating element that is attached by awrap. In order to change or remove the heating element, the user mustattempt to unwrap the heating element from the transderrnal patchwithout disturbing the transdermal patch. This can be particularlydifficult if the user needs to make the change quickly or if the patchis located in a position that makes delicately removing and replacingthe heating element wrap impractical. For example, if the heatingelement were secured to a patch by a wrap that went around a patient'storso, frequent removal of the wrap could require substantial extraeffort and work on the part of the patient and/or the user.

[0010] Another disadvantage of prior art teachings is the cost ofintegrating a heat element with a transdermal patch, particularly forheating elements that have limited uses and applications. If a patientrequires a certain level of heating in one circumstance and a differentlevel of heating in another, then the integrated patch must be removedand an entirely different patch with an appropriate heating level mustbe applied. Alternatives to this would require complex patch designsthat attempt to control or modify the amount of heat generated by theheating element. Thus, using an integrated patch may increasemanufacturing costs significantly. Moreover, modified and integrateddesigns may prove to be less reliable and may be prone to misuse.

[0011] Another disadvantage of the prior art is the potential for abusewhere the heating element neither corresponds to a specific patch nor isintegrated with a particular patch. If a heating patch can be freelyused with any given transdermal device, there is a potential for thepatch to be abused by a patient or misused by the user. For example, thepatient may apply a heating element that induces an absorption rate thatis too fast or delivers too much drug. Conversely, the user may apply aheating element that fails to supply sufficient heat for a particulartreatment. Thus, where the patches do not correspond to the heatingelements used with them, there is a potential for abuse or misuse.

BRIEF SUMMARY AND OBJECTS OF THE INTENTION

[0012] In view of the foregoing, it is an object of at least oneembodiment of the present invention to provide a securable heatingelement compartment with corresponding freely transferrable heatingelement.

[0013] It is another object of at least one embodiment of the presentinvention to provide a heating element advantageously secured to atransdermal drug patch.

[0014] It is another object of at least one embodiment of the presentinvention to provide a transdermal drug patch with a correspondingheating element pouch.

[0015] It is another object of at least one embodiment of the presentinvention to provide a heating element that is securely attached to butfreely removable from a transdermal drug delivery patch.

[0016] It is another object of at least one embodiment of the presentinvention to provide a transdermal drug delivery patch and correspondingheating element that allows a heating element to be used to decrease thetime necessary to reach steady state and that can be convenientlyreplaced with another heating element with different heatingcharacteristics that provide different results,

[0017] It is another object of at least one embodiment of the presentinvention to provide a transdermal drug delivery patch and correspondingheating element that can facilitate treatment of breakthrough pain,and/or that can be regulated to match the body's circadian rhythms,and/or that can provide additional booster drugs when necessary.

[0018] It is another object of at least one embodiment of the presentinvention to provide an electrical heating element advantageously andremovably secured to a transdermal drug delivery patch.

[0019] Additional objects and advantages of the invention will be setforth in the description which follows, and in part will be obvious fromthe description, or may be learned by the practice of the invention. Theobjects and advantages of the invention may be realized and obtained bymeans of the instruments and combinations particularly pointed out inthe appended claims.

[0020] To achieve the foregoing objects, and in accordance with theinvention as embodied and broadly described herein, the presentinvention comprises a securable, heating element compartment with acorresponding, freely-transferrable heating element. The heating elementcompartment may be integrated with or secured to a transdermal drugdelivery patch (drug patch). The heating element compartment provides anarea of restraint that prevents the freely transferrable heating elementfrom being displaced relative to the drug patch to which the heatingelement compartment is secured.

[0021] The freely transferrable heating element limits the likelihoodthat a drug patch will become dislodged or displaced during theplacement, transfer, or replacement of the heating element. Thus, thefreely transferrable heating element is secured proximate to a drugpatch but, nevertheless, is easily removed and replaced with use inconjunction with the heating element compartment of the presentinvention. The heating element does not require an adhesive to besecured to the drug patch, nor does it need to be wrapped or otherwisetied to the patch or patient.

[0022] The heating element can be secured or retained in the area ofrestraint within the heating element compartment using the noveltechniques disclosed herein, or alternatively, techniques known in theart. Novel techniques for restraining the freely transferrable heatingelement include using the top of the heating element compartment toprovide tension and downward pressure upon a heating element within theheating element compartment. Tension or downward pressure may beprovided by sealing at least one edge (or a portion of an edge) of thetop of the heating element compartment to create an area of restraintwithin the compartment disposing a corresponding heating element withinthe heating element compartment. Because the heating element correspondsto the pouch either in relative shape or size (being approximately thesame size and/or shape), the heating element fits snugly into thecompartment and is secured within the heating element compartment in anarea of restraint. The edge of the heating element compartment may besealed and secured to a drug patch or may be sealed and secured to abottom portion of the heating element compartment. The top may beintegrated with the patch or may be secured to the patch or releasablysecured to the patch.

[0023] The heating element compartment also provides a physical barrierlimiting relative displacement of the heating element. In oneembodiment, the heating element is contained within the compartment bysealing and securing at least a portion of an edge of the top. Thesealed edge contains the heating element within the compartment andprevents the compartment from being unintentionally displaced out of thecompartment.

[0024] Another potential means of restraint is the use of materials thathave or create sufficient frictional forces between the heating elementand the heating element compartment to resist the displacement andrestrain the heating element in the compartment when the heating elementexperiences a directional force that would otherwise displace theheating element. Similarly, a clip or slide mechanism may be provided torestrain the heating element as shown in FIGS. 15 and 16. Limitedadhesion or a very light weight adhesive within the heating elementcompartment may also provide a force, for resisting lateral displacementof the heating element.

[0025] The heating element compartment comprises at least a top fordefining the compartment and at least a portion of an edge of the topthat is secured. The edge may be secured to a transdermal drug deliverypatch (drug patch). Alternatively, the edge may be secured to a bottomof the heating element compartment. If the top is secured to the drugpatch, the top side of the drug patch may serve as a “bottom” for theheating element compartment; the top is secured at least along one edge(or a portion of one edge) to the transdernal drug patch. The top andbottom or the top and the drug patch define a heating elementcompartment that is secured, or is capable of being secured to or isintegrated with a transdermal drug patch. Thus, the top is secured tothe patch or alternatively, the top is secured to a bottom to form apouch.

[0026] The top may have a shape that corresponds to the shape and sizeof the heating element to facilitate the restraint of the heatingelement in the restraining area of the heating element compartment. Asshown in FIGS. 1 through 20, the top may be any number of shapes andsizes. The shape of the top (as well as the heating element) may beoval, circular or semicircular, polygonal, or any other number ofshapes. At least one edge or a portion of one edge of the top must besealed to the drug patch, or in the alternative, to a bottom sheet toform a heating element compartment or a pouch.

[0027] The top may be manufactured from any number of materials known inthe art. The qualities of the material may affect the design of thepouch and the corresponding heating elements, and may affect or evendictate the type of treatment with which the pouch and heating elementcan be used. The top may be air permeable, air impermeable, orselectively permeable. It may be translucent, transparent, or be aparticular color. The top may have inherent insulative properties or maybe designed and manufactured to have enhanced insulative properties. Thetop and/or the compartment defined by the top may also protect andshield the heating element once the heating element is in place. The topmay be rigid, but is preferably flexible and elastic.

[0028] Some of the embodiments of the present invention require thatoxygen or air be able to pass into the heating element compartment,others do not. If the heating element does not require air to passthrough into the heating element compartment in order to function, thetop of the compartment can be made of a material which is airimpermeable. Thus, the materials used to form the heating elementcompartment will depend in part upon the type of heating elementselected. Characteristics of the pouch's construction may vary dependingupon the use of the pouch, but the pouch should be securable orintegrated with the heating patch and should allow the heating elementor the pouch contents to be freely transferred into or out of the pouchat a desired time.

[0029] In one embodiment, the heat from the heating element activatesadhesive on a portion of the top, such as the entry space into thepouch, and seals the pouch when that portion is closed. When the heatingelement stops generating heat, the adhesive is deactivated and the pouchopens or is more readily opened along that portion.

[0030] The freely transferrable heating element of the present inventionis a device capable of delivering controlled heat to the transdermaldrug delivery patch and/or the patient's skin The heating element is ofa size and shape that corresponds to the securable heating elementcompartment. The freely transferrable heating element can be placed inthe heating element compartment and remains secured in the area ofrestraint relative to the drug patch. The heating element compartmentreduces the likelihood that the freely transferable heating element willbe unintentionally dislodged until the heating element is intentionallyremoved from the compartment and drug patch. The heat from the heatingelement can be generated using a chemical reaction, such as an oxidationreaction, electrical heat, or other means of generating controlledthermal heat. Other methods for generating heat, such ascrystallization, microwave, or infrared heat, are also contemplated.

[0031] The heating element may provide insulation to the drug patch andskin, and may be designed to provide additional insulation to maintain ahigher, controlled temperature. The heating element shapes and sizes maycorrespond to the shape and sizes of the heating element compartment andhave substantially similar dimensions. The heating element is designedto allow the heating element to be placed within the heating elementcompartment with relative ease and to be removed from the compartmentwith relative ease, but nonetheless remains secured in the compartmentto reduce the likelihood the heating element will be unintentionallydisplaced from the compartment or separated from the patch.

[0032] The heating element of the present invention can provide heat fora particular duration. Where the heating element is an electricalheating element the duration of the heat may be any amount of timelimited only by the ability of the battery or electric power supply tosupply current to the electrical heating element. The electrical heatingelement can pulse on and off as necessary and the replacement drugpatches can be supplied as frequently as necessary. Heating elementsthat use chemical reactions can be designed, manufactured to provideheat for a given duration.

[0033] The heating element provides controlled heating. Controlledheating allows the user to provide a level of heat that results in anincrease in temperature to a predetermined or prescribed range.Controlled heating is preferable to heating devices that are notcontrolled. If the heating element is incapable of delivering controlledheat, it becomes difficult to regulate the amount of drug beingdelivered, and the potential for overdose or underdose is significantlyincreased. Similarly, the patient's skin may be blistered or burned byuncontrolled heat. By being secured in the area of restraint within thecompartment attached to the patch, the heating element provides uniform,controlled heating.

[0034] One embodiment of the heating element comprises a chamber definedby air impermeable walls. The chamber is defined by a bottom wall, a topwall and side walls. The heating element preferably comprises thecomposition of activated carbon, iron powder, sodium chloride, water,and optionally, sawdust, which is disposed in the chamber. The top wallis preferably a flexible air impermeable material having a plurality ofholes therethrough. The top wall may be an air permeable membrane or anair impermeable material with a plurality of holes. The top wall canhave at least one covering for the plurality of holes or can have acovering to prevent air from passing through the air permeable membrane.In the embodiment having a plurality of holes in the top wall, the holescan be selectively covered and uncovered. By selectively covering anduncovering the holes in the top wall, the heat and duration may bevaried and administered as desired.

[0035] The present invention can be used to increase the serumconcentration of the drug delivered by the drug patch by a desiredamount. For example, it may be necessary in treating a particularpatient to increase the serum concentration of the drug delivered by thedrug patch by 10% over the normal serum concentration as established bythe drug patch's steady state. The present invention allows a controlledincrease in temperature, which can be maintained at the increased leveland if desired, returned to the original steady state level withoutchanging the drug patch used to deliver the drug. Similarly the patientmay find that an increase of a certain percentage is necessary forcertain activities. A patient may need an increase in a drug serumconcentration level during a period of increased physical activity ormay require less drug during a period of rest. The present inventionprovides the capacity to conveniently adjust drug serum concentrationlevels by applying controlled heat and does so in a way that limits thechances that the drug patch will be dislodged or compromised during theapplication.

[0036] The securable heating element compartment can be integrated witha specially designed drug patch, or used in conjunction with drugpatches known in the art. Where the drug patch is integrated with theheating element compartment, it may be advantageous to only use a top toform the securable compartment. Where the patch is a pre-existing patchor one available in the market, the top sheet may need to be combinedwith a bottom sheet to form a securable heating element compartment. Thesecurable heating element compartment should be of a shape and size tocorrespond to the specific drug patch.

[0037] The heating element should be of a shape and size to conform orcorrespond to the heating element compartment and the heating elementshould be designed for safe and effective use with a particular type ofdrug patch. For example, the freely transferable heating elementsdesigned for use with transdermal fentanyl may have a particular sizeand shape and color. For a patch with a different drug, such as atestosterone patch, the colors and shapes of the heating element may bedifferent than those for fentanyl. Thus, it is preferable that theshapes and sizes of the securable heating element compartments, and inparticular the heating elements, be designed and manufactured so thatthe compartments and heating elements designed for use with one type ofdrug patch are not readily useable or interchangeable with another typeof drug patch. The color may indicate the type of drug with which thesecurable compartment and heating element should be used and may alsoindicate the desired effect the compartment and heating element areintended to have. If a securable compartment and heating element isdesigned for a particular drug patch and if use of the heating elementwith a different drug patch could cause harm or overdose, the heatingelement and corresponding compartment should be designed so as not to becompatible with the drug patches that could result in such harm.

[0038] The present invention allows for heating elements and otherarticles to be placed proximate to a transdermal drug patch using aheating element compartment or pouch. For example, the compartment orpouch could be used to retain various devices which could beadvantageously placed proximate to the drug delivery patch, such asiontophoresis devices, timing devices, notification or reminder devices,any type of heating and/or cooling mechanisms, patient or patchmonitoring devices, alarms, timers, watches, microprocessors,thermostats, thermometers, use indicators, and potentially and variousnovelty items such as toys for encouraging the use of the deliverysystem by children.

[0039] It is understood that a considerable variety of drug classes andspecific drugs can be used with the present invention. Drug classes mayinclude without limitation androgens, estrogens, nonsteroidalanti-inflammatory agents, antihypertensive agents, analgesic agents,antidepressants, antibiotics, anticancer agents, local anesthetics,antiemetics, antiinfectants, contraceptives, antidiabetic agents,steroids, anti-allergy agents, anti-migraine agents, agents for smokingcessation, and anti-obesity agents. Specific drugs include withoutlimitation nicotine, testosterone, estradiol, nitroglycerine, clomidine,dexamethasone, wintergreen oil, tetracaine, lidocaine, fentanyl,sufentanil, progesterone, insulin, vitamin A, vitamin C, vitamin E,prilocaine, bupivacaine, sumatriptan, dihydroergotamine, andscopolamine.

BRIEF DESCRIPTION OF THE DRAWINGS

[0040] The foregoing and other objects and features of the presentinvention will become more fully apparent from the following descriptionand appended claims, taken in conjunction with the accompanyingdrawings. Understanding that these drawings depict only typicalembodiments of the invention and are, therefore, not to be consideredlimiting of its scope, the invention will be described and explainedwith additional specificity and detail through the use of theaccompanying drawings in which:

[0041]FIG. 1 shows a top view of a drug patch with a securablecompartment and a freely transferrable heating element;

[0042]FIG. 2 is a cross section of the drug patch with the securablecompartment and freely transferrable heating element;

[0043]FIG. 3 shows an embodiment of a two-sided top with at least oneedge suitable for sealing;

[0044]FIG. 4 shows a top having three edges with at least two edgessuitable for sealing;

[0045]FIG. 5 shows a four-sided top having two edges suitable forsealing; FIG. 6 shows a top having four edges with two edges suitablefor sealing;

[0046]FIG. 7-A shows a five-sided top with three edges suitable forsealing;

[0047]FIG. 7-B shows a one-sided top with a portion of an edge suitablefor sealing;

[0048]FIG. 8 shows a cross section of the securable compartment with afreely transferrable heating element secured on a heating patch, theheating element and the compartment having additional insulativeproperties;

[0049]FIG. 9 shows a top defining an opening;

[0050]FIG. 10 shows a top defining a plurality of openings;

[0051]FIG. 11 shows a top defining an opening having a semi-permeablemembrane covering said opening;

[0052]FIG. 12 shows a top that is an air permeable membrane;

[0053]FIG. 13 shows a top that has additional insulative properties;

[0054]FIG. 14 shows an electrically operated heating element in asecurable compartment attached to a transdermal drug patch;

[0055]FIG. 15 shows a top view of securable compartment havingattachment clips;

[0056]FIG. 16 shows a top view of a securable compartment havingattachment clips in which the disk is held in place by the clips;

[0057]FIG. 17 is a partial cutaway of a securable compartment with afreely transferrable heating element retained in an area of retainingsecured to a drug delivery patch;

[0058]FIG. 18 shows one embodiment of an electric heating element;

[0059]FIG. 19 shows an embodiment of an exothermic heating element; and

[0060]FIG. 20 shows another embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0061] It will be readily understood that the components of the presentinvention, as generally described and illustrated in the figures herein,could be arranged and designed in a wide variety of differentconfigurations. Thus, the following more detailed description of theembodiments of the system and method of the present invention, asrepresented in FIGS. 1 through 20, is not intended to limit the scope ofthe invention, as claimed, but is merely representative of the presentlypreferred embodiments of the invention.

[0062] The presently preferred embodiments of the invention will be bestunderstood by reference to the drawings, wherein like parts aredesignated by like numerals throughout.

[0063] As shown in FIG. 1, in one embodiment, the present inventioncomprises a drug delivery patch 60, a securable heating elementcompartment 80, and a freely transferrable heating element 100 retainedin compartment 80. The drug patch 60, with a heating element compartment80 and an electric heating element 100, is placed upon the skin of apatient in need of transdermal delivery of a drug where heating element100 delivers controlled heat to the patient's skin and the drugformulation and the drug delivery patch 60. The controlled heatincreases the absorption of the drug through the skin into the systemiccirculation of the patient. Controlled heat on the patient's skin anddrug patch 60 results in an increased absorption rate that allows thepatient to obtain a steady state concentration in the systemiccirculation more quickly than the patient could without the heatingelement.

[0064] After the heating is finished, heating element 100 may beremoved, but is preferably left inside securable heating elementcompartment 80 in order to provide insulation to the administrationsite. Heating element 100 can be replaced with another freelytransferable heating element 100 if necessary in order to provideadditional heat. The additional heat may be provided to further increasethe concentration level of the steady state, or alternatively, may beprovided to give the patient additional drug beyond a desired steadystate. After establishing a steady state, original heating element 100can be replaced by a different kind of heating element 100, ifnecessary, and a different level of controlled heat may be applied tothe patient's skin, the dermal drug patch 60, and the drug formulationin order to cause a sharp increase in the drug concentration above thesteady state. Such a dramatic rise in the increase may help to improve apatient's treatment such as by mimicking natural circadian patterns,providing additional relief for breakthrough pain, or providingadditional drug when a patient has a heightened need (urgent need) or isexperiencing withdrawal pains or cravings (breakthrough cravings).

[0065] In one embodiment of the present invention, controlled heating ofthe heating element is provided by an oxidation reaction. As shown inFIG. 19, the heating element 100 comprises side wall 106 defined by a ⅛inch thick rectangular foam tape (2 layers of No.1779 {fraction (1/16)}″white foam tape, 3M Corporation, Minneapolis, Minn., USA) with an outerdimension of about 2.25 inches by 4 inches with an opening thereinhaving an inner dimension of about 1.75 inches by 3.5 inches, a bottomwall 102 comprising rectangular medical tape (No. 1525L plastic medicaltape, 3M Corporation, Minneapolis, Minn., USA) of a dimension of about2.25 inches by 4 inches with a non-adhesive side attached to the bottomof side wall 106, and a top wall 104 comprising a rectangular {fraction(1/32)} inch thick foam tape (No. 9773 {fraction (1/32)}″ tan foam tape,3M Corporation, Minneapolis, Minn., USA) with forty-five holes 114(diameters approximately 0.9 mm, in a 5 by 9 pattern with about 7.5 mmto 8.0 mm center spacing) therethrough. Side wall 106, bottom wall 102,and top wall 104 define a chamber. The holes 114 of top wall 104 may becovered by an air permeable membrane 116 comprising a porous membrane(No. 9711 microporous polyethylene film—CoTran™, 3M Corporation,Minneapolis, Minn., USA) disposed between the top wall 104 and thetemperature regulating mechanism 108. Side wall 106, bottom wall 102,and top wall 104 all have ⅛″ rounded comers. Heat generating component108 disposed in the chamber comprises a mixture of activated carbon (HDCgrade—Norit Americas, Inc., USA), iron powder (grade R1430—ISPTechnologies, USA), saw dust (Wood Flour, Pine - Pioneer Sawdust, USA),sodium chloride and water in the weight ratio of approximately5:16:3:2:6 weighing approximately 16.5 grams. Heating element 100 issealed in an air-tight container immediately after fabrication.

[0066] In one embodiment, the invention entails the integral attachmentof heating element compartment 80 (or pouch 80) to the top side of atransdermal drug delivery patch 60 for the purposes of affixingcontrolled heating element 100, such as a heating disc 100, to drugpatch 10. Drug patch 60 may be a reservoir or matrix (monolith) patch.The compartment or pouch 80 is formed by securing a heating elementcompartment top 82 to a drug patch 60. Top 82 has at least one edge 84with at least a portion 86 of edge 84 being secured or sealed to drugpatch 60. Pouch 80 may be made of a variety of materials. Top 82 ofpouch 80 may be attached to drug patch 60 along at least portion 86 ofedge 84 by any of several means such as heat-sealing, RF-welding, or theuse of any variety of adhesive. Pouch 80 is used to house or containheating element 100, (such as a disposable, air-activated, chemicalheating or disc to enhance the delivery of drugs through the skinmanufactured by ZARS) holding the heating element 100 in direct contactwith drug patch 60. The perimeter of “marsupial” pouch 80 is sealed todrug patch 60 except for an entry 88 large enough to slide heatingelement 100 in and out of pouch 80. Sealed edges 86 near entry 88 of thepouch 80 provide a smooth pathway for easy insertion and removal ofheating element 100. (See FIG. 19). Pouch 80 defines at least oneopening 90 or a number of smaller openings 90 across its surface inorder to allow oxygen to enter and activate heating element 100.

[0067] The active ingredient in transdermal drug patch 60 may be any ofa number of drugs, such as, but not limited to, fentanyl, testosterone,estradiol, scopolamine, nicotine, nitroglycerin, local anesthetics etc.Transdermal drug patch 60, attached pouch 80, top 82, and heatingelement 100 may be any of a variety of different shapes, such as, butnot limited to, a square, rectangular, circular, oval, triangular, asshown in FIGS. 1-20.

[0068] The use of different heating elements 100 with different heatingcharacteristics can provide important advantages in treatments. Forexample, with the transdermal delivery of fentanyl, the application of a4-hour heating element with a temperature of 42-44° C. has been found todecrease the time required for patch 60 to reach steady-state serumfentanyl concentrations from 14-18 hours to 3-4 hours. Aftersteady-state drug levels have been achieved, patients often experienceshort episodes of increased pain known as breakthrough pain. A 5-minuteapplication of similar heating element 100 has been found to increaseserum fentanyl levels by more than 60 percent. This increase is morethan sufficient to combat breakthrough pain. Hence, at least twodifferent types of heating elements 100 or discs 100 are useful inconjunction with the transdermal fentanyl patch 60; one for reducing theonset time to steady-state levels and one for combating breakthroughpain.

[0069] Heating elements 100 of different sizes and shapes and differentheating temperatures and durations may be housed in marsupial pouch 80.Heating patches 100 or discs 100 may be color-coded in order to indicatedifferent heating temperatures and durations for different uses. Forexample, the onset heating element 100 might maintain a temperature of42-44° C. for 4-hours and might be blue. The breakthrough heatingelement 100 might maintain a temperature of 42-44° C. for 5-20 minutesand might be green.

[0070] In the case of fentanyl, fentanyl patch 60 may be packaged with ablue onset heating element 100 already housed in marsupial pouch 80.Thus, when patch 60 is applied, the heating begins and a shorter onsettime to steady-state is achieved. After several hours, when heatingelement 100 has expired and steady-state has been reached, the heatingelement 100 may be left in marsupial pouch 80 in order to provide alevel of insulation, which may protect drug patch 60 from variations inambient temperature. Later on, when an episode of breakthrough pain isexperienced, blue onset heating element 100 may be removed frommarsupial pouch 80 and a green breakthrough heating element 100 may beinserted into pouch 80. As heating element 100 dies out on its own afterits prescribed heating duration, it is not necessary to remove it atspecified time intervals. Rather, heating element 100 may be left inmarsupial pouch 80, if desired, until a new breakthrough heating element100 is needed.

[0071] There are several significant advantages to “marsupial” pouchtechnology. Since marsupial pouch 80 is directly attached to transdermaldrug patch 60, there is no need to use adhesive to attach heatingelement 100 to drug patch 60, which would increase the likelihood ofremoving drug patch 60 upon removal of the heating element 100.Marsupial pouch 80 provides excellent contact between heating element100 and drug patch 60. Marsupial pouch 80 limits the risk of abuse ofheating patch 60 with other drug patches for which it is not indicatedand with which it has not been studied. As heating elements 100, ordiscs 100, are preferably not adhesive, they cannot be used with anydrug patch, but only with those that have a corresponding pre-attachedmarsupial pouch 80 for housing drug patch 60. Marsupial pouch 80simplifies the process of using several different types of heatingelements 100 (for example, onset and breakthrough elements) since it issimple and easy to remove and replace heating elements 100. Heatingelements 100 may have a tab on one end to facilitate easy insertion andremoval.

Example 1

[0072] In one example, an embodiment of the present invention is usedfor dermally administrating nicotine for suppressing a patient'snicotine cravings. A user (a patient or caregiver) administers anicotine patch 60 with a freely transferrable heating element 100 in aheating element compartment 80 secured to patch 60. After just a fewhours, the patient should obtain a steady state nicotine concentrationin the blood stream sufficient to suppress a baseline nicotine craving.When the patient starts to have an episode of increased nicotine craving(a breakthrough craving), the user replaces freely transferrable heatingelement 100 with a second, different transferrable heating element 100,the second heating element having different heating characteristics.Second heating element 100 is placed in compartment 80. Second heatingelement 100 may use an exothermic reaction to generate heat. The heatcreated by second heating element 100 lasts for at least 15 minutesbefore the exothermic reaction exhausts second heating element 100. Theheat increases the transport of nicotine across the skin and increasesthe blood flow in the tissues under nicotine patch 60, which carries thenicotine stored in tissues under patch 60 into the systemic circulationat increased rates. As a result, the patient gets a rapid increase inblood nicotine concentration to treat the surge of the nicotine craving.After the heating, the absorption rate gradually declines to deliver thesteady state nicotine concentration in the blood stream.

Example 2

[0073] Another example of using an embodiment of the present inventionfor dermally administering testosterone to increase and optimize theamount of drug delivered comprises a user placing a testosterone patch60, such as a one day dermal testosterone patch (EG Androdermn²⁰⁰produced by TheraTech, Inc. of Salt Lake City, Utah, USA) on the skin ofthe patient. Patch 60 can be applied to the skin at night, for example,around 10:00 p.m. However, in order to raise the steady stateconcentration of the testosterone quickly, the user may apply a freelytransferrable heating element 100 to a heating element compartment 80secured to testosterone patch 60. Heating element 100 is designed toprovide heat for a desired period of time in order to allow the serumconcentration of testosterone to reach a steady state more rapidly thanit would without heating element 100. When heat from heating element 100is terminated, heating element 100 may provide a measure of insulationto maintain an increased level of absorption from patch 60 or may befreely removed from compartment 80.

[0074] Testosterone patch 60 can be worn or applied at night, forexample, around 10:00 p.m. However, if the patient does not get asufficient dosage of testosterone by the next day, the user can apply asecond, different heating element 100 into secured compartment 80 ofpatch 60. Second heating element 100 can provide increased temperatureto patch 60 and the skin and the tissues under the skin and therebysignificantly increase the absorption of testosterone. Additionally, theheat may promote the effectiveness of a permeation enhancer in the drugformulation of patch 60. The ultimate result is that the patient getssufficient testosterone from patch 60 in an efficient manner. Theefficient use of heating element 100 may allow the reduction ofpermeation enhancer concentration in the drug formulation of patch 60.Permeation enhancers are sometimes associated with significant skinirritation.

Example 3

[0075] The present invention can also be used to administer a drugtransdermally that otherwise would have a diffusion coefficient or apermeability coefficient across a rate limiting membrane 62 of patch 60that would be disadvantageously low. A user places a patch containing adrug onto the skin of the patient and after waiting for a period of timedetermines that the administration requires a higher concentration ofdrug in the patient's blood stream to properly treat the patient'scondition. The user can remove freely transferrable heating element 100and replace it with a second, different freely transferrable heatingelement 100 having heating characteristics that facilitate increasedabsorption of the drug. Increased temperature provided by second heatingelement 100, for example, may increase the diffusion coefficient of theactive ingredient in the formulation and/or increase the permeabilitycoefficient of the drug across the rate limiting membrane of patch 60.The overall rate at which the active ingredient enters the body wouldthereby also increase and in turn, increase the concentration of theactive ingredient in the patient's blood stream.

Example 4

[0076] The present invention can be used to decrease the onset time of adrug from a transdermal drug patch 60. A user places patch 60 on apatient's skin. Patch 60 contains a freely transferrable heating element100 secured in heating element compartment 100 on patch 60. The heatallows the drug formulation in transdermal drug patch 60 to be absorbedmore quickly through the skin. However, if the user determines that afaster onset time is necessary for proper treatment of the patient, theuser can replace the initial heating element 100 with a second,different freely transferrable heating element 100 having differentheating characteristics, for example, generating higher temperatures.The increased temperature allows the drug to be absorbed into thepatient's systemic circulation more quickly and if sustained over asufficient amount of time results in a quicker onset of the drug. Afterobtaining onset in a shortened period of time, second heating element100 with the higher temperature can be left in place for insulativeeffect or removed or replaced with a heating element 100 that allowspatch 60 to deliver the drug at a more typical steady state. Theimportant advantage provided by this approach is that the onset time ofpatch 60 can be shortened without significantly altering the patch'ssteady state delivery rate.

Example 5

[0077] Another example of the present invention is used to provide adeeper penetration of a drug formulation into a patient's tissues. Theuser places a transdennal drug patch 60 on the skin of the patient. Drugpatch 60 contains a freely transferrable heating element 100 in aheating element compartment 100 secured to patch 60. Patch 60 heats thepatient's skin and heating element 100 for a period of time. The drugfrom transdermal patch 60 is absorbed into the tissues beneath andproximate to drug patch 60. Heating element 100 facilitates theabsorption of the drug into the tissue.

[0078] If it is determined that the drug is not penetrating beneath thesurface of the skin deeply enough for proper treatment, heating element100 can be removed and replaced with a second, different freelytransferrable heating element 100, which provides different heatingcharacteristics, such as increased duration or increased temperature.For example, as second heating element 100 increases the temperature ofthe drug formulation and the tissues around drug patch 60, the heatdrives the drug further into the skin and allows for deeper penetration.

[0079] If desired, after the drug has reached a penetration levelsufficient for the treatment, second heating element 100 can be removedand replaced with the original heating element 100 or another freelytransferrable heating element 1 00 having heating characteristics moresuited toward delivering a drug at a desired rate.

Example 6

[0080] Another example of the present invention comprises replacing anoriginal heating element 100 with a second, different heating element100 to increase solubility of the drug in formulation. A drug deliverypatch 60 may have a drug formulation with a certain solubility of thedrug in the drug formulation. The solubility rate may be appropriate fora given treatment and provide the drug to the skin for absorption at aparticular desired rate. Solubility of the drug may be dependent uponthe heat applied to the drug formulation by an initial freelytransferrable heating element 100. In the present invention, initialheating element 100 can be removed and replaced with a second,different, freely transferrable heating element 100 that providesdifferent heating characteristics. Second heating element 100 maygenerate increased heat so that the solubility of the drug in the drugformulation is higher. Because the increased temperature increases thesolubility of the drug compound in the formulation, more drug compoundcan be dissolved in the formulation, which may yield a higher drivingforce for the transdermal permeation of the drug compound. Ultimately,more of the drug can enter the patient's systemic circulation.

Example 7

[0081] As mentioned above, the possible heating elements are not limitedto the exothermic reaction mixture of iron powder, activated carbon,salt, water, and sawdust, as discussed above. FIG. 18 illustrates anelectric heating element 200 comprising an electric heating element 202surrounded by a bottom wall 102, a top wall 104, and side walls 152 Theside walls 152, preferably, extend a distance below the bottom wall 102to define a cavity 154. It is understood that the electric heatingelement 202 does not have to have the side walls 152 forming a cavity154.

[0082] The bottom wall 102 and the side walls 152 are preferably made ofa flexible non-air permeable material, such as non-air permeableclosed-cell foam material. A portion of the bottom of the heatingelement 200 includes an adhesive material 112 on the bottom of the sidewalls 152 and, preferably, includes a second adhesive material 156 inthe bottom of the bottom wall 102, wherein the second adhesive material156 is preferably less adhesive than the adhesive material 112. Theelectric heating element 202 preferably comprises a flexible resistorplate that can generate heat when supplied with an electric currentthrough traces 206, 208. The electric current is preferably suppliedfrom a battery 212 attached to a control mechanism 214, and anelectronic switch 216. The battery 212, the control mechanism 214, andthe electronic switch 216 are preferably attached to the top surface ofthe top wall 104. The electric heating element 202 is activated bytriggering the electronic switch 216 which begins the flow of electriccurrent from the battery 212 to the electric heating element 202. Atemperature sensor 218, such as a thermistor, is preferably attached tothe bottom of the bottom wall 102 and sends a signal (corresponding tothe temperature at the bottom of the bottom wall 102) through electrictrace 222 to the control mechanism 214. The control mechanism 214regulates the flow of current to the electric heating element 202, sothat the electric heating element 202 quickly brings the temperature ata contact surface between the bottom wall 102 and a top of a drug patch(not shown) to a pre-determined level and maintains the temperature atthat pre-determined level. The following features may be incorporatedinto the control mechanism 214: 1) a mechanism that allows a physicianor care giver set the length of each heating period for each patient,which allows the physician to limit the heating, and hence the extradrug that the patient can get based on the conditions of the patient; 2)a mechanism that allows the physician or care giver to set the minimumtime between the heating periods, and hence how often the patient canget the extra drug through increase heat; 3) a mechanism that allows thephysician or care giver to set a predetermined temperature; and/or 4) amechanism that allows the physician or care giver to control the heatingtemperature profile, such as gradually increasing heating temperature ordecreasing temperature over a pre-determined period of time. Thesefeatures can potentially give a prior art drug patch a variety ofcontrol options for the physician and/or the patient on the quantity andtiming of the delivery of extra drug. The heating element can be freelytransferable into and out of a heating element compartment or pouch.

[0083] Battery 212, control mechanism 214, and electric switch 216 maybe attached to the heating element or the drug delivery patch to whichthe heating element is secured. Alternatively, battery 212 and controlmechanism 214 may be worn separately. For example, a detached battery212 and control mechanism 214 are shown in FIG. 14.

[0084] In another embodiment, electric heating compartment 202 may beactivated by the automatic triggering of electronic switch 216 andallowing a flow of electric current from the battery through the heatingelement. Temperature sensor 218 that provides precise regulation of theheat generated in the heating element may also provide an additionalcontrol mechanism for the duration of the heat generated by electricheating element 200. The electric heating element can be combined with amicroprocessor 230 to provide highly accurate and highly regulatedtemperature control. For example, microprocessor 230 can regulate whenthe heating element 200 is turned on, its temperature, and when heatingelement 200 is turned off. Electric heating element 200 can be freelytransferred from heating element compartment 80 secured to patch 60 andreplaced with different electric heating element 200 or some otherheating elements 100.

Example 8

[0085] One of the distinct advantages of the present invention is theability to use various types of heating elements 100 to generate heatfor the delivery of the drug through transdermal patch 60. For example,a patient may have applied a dermal drug delivery patch 60 with a freelytransferable heating element retained in a compartment secured to thepatch. Heating element 100 may be an electric heating element 200 havingan electric current supplied by a battery 212. In the event that theelectric heating element 200 malfunctions or battery 212 for the patchruns out of current, electric heating element 200 can be easily removedand replaced with a different electrical heating element 200 or with adifferent heating element 100, such as a heating element using heatgenerated from an exothermic chemical reaction. The ability to changefrom electrical to exothermic chemically generated heat may beparticulary advantageous where the activities of the patient prohibit ormake impractical the use of a given type of heating element. Where apatient is intending to engage in an activity that would not beconducive to the use of an electrical heating element, the patient mayreplace the electrical heating element with the exothermic chemicalheating element or some other type of heating element 100.

Example 9

[0086] In an alternative embodiment of the present invention, a dermaldrug delivery system comprises a heating element structure 302releasably secured to a patient's skin. The heating element structurecomprises a heating element 300 and a top side 304 having at least aportion of an edge secured to the skin or alternatively secured to abottom side that is secured to the skin. Alternatively, at least twowalls extending from the top side toward the bottom side may be attachedto a patient's skin. Heating element structure 302 defines a compartmentin which is provided an area of containment beneath the bottom side ofthe heating element 300. A freely transferable drug delivery patch 310may be placed into the compartment beneath heating element 300. The drugdelivery patch 310 is secured in the area of containment and maintainscontact with the patient's skin to deliver the drug in the drug patch310. Heat from heating element 300 is used as disclosed in theapplication to improve the administration of the drug from drug patch310. Thus heating element structure 302 forms a drug delivery patchcompartment and provides heat to drug delivery patch 310.

[0087] If heating element 300 is connected to a microprocessor, a widevariety of drug delivery patches can be used in combination with heatingelement 300, which can be adjusted and programmed to provide heat atdesired times and for desired durations in accordance with the drugbeing used. Patch 310 that is used with heating element 300 could bedesigned to have identification information on patch 310 that indicatesto the user the appropriate heat settings for heating element 300.Through the use of the microprocessor identification information is readby a reading device such as an optical scanner and the microprocessorautomatically sets appropriate beating levels.

Example 10

[0088] Another example of the present invention comprises inserting adevice other than a freely transferable heating element into the drugdelivery pouch. The heating element compartment provides the user theopportunity to place various devices proximate to the heating patchwhich can assist in dermal drug delivery. For example, an iontophoresisdevice can be secured to a heating patch using the pouch of the presentinvention. The iontophoresis device can apply a positive current from anelectrode to a drug formulation on the skin that will drivepositively-charged ions away from the electrode and into the skin.Alternatively a negative current can be applied to influencenegatively-charged ions. Current variations from the iontophoresisdevice will influence and increase the iontophoretic effect in drugdelivery. Thus, an iontophoresis device can be placed in the heatingelement compartment in place of the heating element.

Example 11

[0089] The present invention is not limited to devices which increasetemperature. A cooling element may likewise decrease the temperature orcool the drug formulation, the drug delivery patch, and the patient'sskin. Cooling the patient's skin may slow drug delivery in a manner thatis advantageous for a given treatment. For example, the presentinvention can be used to increase the onset time of the drug from atransdermal drug patch 60. A user places patch 60 on a patient's skin.Patch 60 contains a freely-transferrable cooling element 100 secured incooling compartment 100 on patch 60. The cooling element 100 is capableof cooling the drug patch 60 and the patient's skin. The cooling effecton the drug formulation in the drug patch 60 slows the absorption of thedrug through the patient's skin. By slowing the absorption from the drugpatch 60, the cooling element 100 reduces the serum concentration leveland thereby increases the onset time of the drug.

[0090] The present invention may be embodied in other specific formswithout departing from its spirit or essential characteristics. Thedescribed embodiments are to be considered in all respects only asillustrative and not restrictive. The scope of the invention is,therefore, indicated by the appended claims, rather than by theforegoing description. All changes which come within the meaning andrange of equivalency of the claims are to be embraced within theirscope.

What is claimed is:
 1. Transdermal drug delivery system comprising adermal drug delivery patch; a heating element compartment securable tothe dermal drug delivery patch; and a freely transferrable heatingelement securable within the heating element compartment.
 2. The drugdelivery system of claim 1, wherein said heating element compartment isdefined by a top having at least one edge sealed to a bottom.
 3. Thedrug delivery system of claim 1, wherein said heating compartment isdefined by a top having at least a portion of one edge sealed to dermaldrug delivery patch.
 4. The drug delivery system of claim 1, whereinsaid heating element compartment further comprises a top having at leastone opening for permitting oxygen to flow into said heating elementcompartment.
 5. The drug delivery system of claim 1, wherein saidheating element compartment defines an entry for freely transferringsaid heating element into and out of said heating element compartment.6. The drug delivery system of claim 1, wherein said heating elementcompartment provides an area for restraining said heating element. 7.The drug delivery system of claim 1, wherein said heating element isretained within said compartment using tension.
 8. The drug deliverysystem of claim 1, wherein said heating element is retained within saidcompartment using friction.
 9. The drug delivery system of claim 1,wherein said heating element is retained within said compartment usingan attachment clip.
 10. The drug delivery system of claim 1, whereinsaid heating element is retained within said compartment using a verylight adhesive for preventing lateral movement.
 11. The drug deliverysystem of claim 1, wherein said top of said heating compartment providesat least one sealed edge for containing said heating element within saidcompartment.
 12. The drug delivery system of claim 1, wherein saidheating element provides heat using an oxidation reaction within saidheating element.
 13. The drug delivery system of claim 1, wherein saidheating element corresponds in size and shape to said heating elementcompartment.
 14. The drug delivery system of claim 1, wherein saidheating element provides controlled heat.
 15. The drug delivery systemof claim 1, wherein said heating element is an electric heating elementhaving an electronic control mechanism.
 16. The drug delivery system ofclaim 1, wherein said heating element is designed to provide insulativeproperties to the drug delivery system.
 17. The drug delivery system ofclaim 1, wherein said heating element is an onset heating element. 18.The drug delivery system of claim 1, wherein said heating element is abreakthrough pain heating element.
 19. The drug delivery system of claim1, wherein said heating element is a breakthrough craving heatingelement.
 20. The drug delivery system of claim 1, wherein said heatingelement is a steady state heating element.
 21. The drug delivery systemof claim 1, wherein said heating element is a breakthrough effectheating element.
 22. A method for delivering a drug transdermallycomprising the steps of: placing a dermal drug delivery patch upon apatient's skin at an administration site; securing a heating elementcompartment to said dermal drug delivery patch; and disposing a freelytransferrable heating element within the heating element compartment.23. The method of claim 22, wherein said heating element compartment isdefined by a top having at least one edge sealed to a bottom.
 24. Themethod of claim 22, wherein said heating compartment defined by a tophaving at least a portion of one edge sealed to the dermal drug deliverypatch.
 25. The method of claim 22, wherein said heating elementcompartment further comprises a top having at least one opening forpermitting oxygen to flow into said heating element compartment.
 26. Themethod of claim 22, wherein said heating element compartment defines anentry for freely transferring said heating element into and out of saidheating element compartment.
 27. The method of claim 22, wherein saidheating element compartment provides an area for restraining saidheating element.
 28. The method of claim 22, wherein said heatingelement is retained within said compartment using tension.
 29. Themethod of claim 22, wherein said heating element is retained within saidcompartment using friction.
 30. The method of claim 22, wherein saidheating element is retained within said compartment using an attachmentclip.
 31. The method of claim 22, wherein said heating element isretained within said compartment using a very light adhesive forpreventing lateral movement.
 32. The method of claim 22, wherein saidtop of said heating compartment provides at least one sealed edge forcontaining said heating element within said compartment.
 33. The methodof claim 22, wherein said heating element provides heat using anoxidation reaction within said heating element.
 34. The method of claim22, wherein said heating element corresponds in size and shape to saidheating element compartment.
 35. The method of claim 22, wherein saidheating element provides controlled heat.
 36. The method of claim 22,wherein said heating element is an electric heating element having anelectronic control mechanism.
 37. The method of claim 22, wherein saidheating element is designed to provide insulative properties to the drugdelivery system.
 38. The method of claim 22, wherein said heatingelement is an onset heating element.
 39. The method of claim 22, whereinsaid heating element is a breakthrough pain heating element.
 40. Themethod of claim 22, wherein said heating element is a breakthroughcraving heating element.
 41. The method of claim 22, wherein saidheating element is a steady state heating element.
 42. The method ofclaim 22, wherein said heating element is a breakthrough effect heatingelement.
 43. The method of claim 22, further comprising the steps ofremoving said heating element from the heating element compartment andreplacing said heating element with a freely transferrable secondheating element in the heating element compartment.
 44. The method ofclaim 43, further comprising the steps of heating said dermal drugdelivery patch and the skin of a patient with said second heatingelement to provide faster onset.
 45. The method of claim 43, furthercomprising the steps of heating said dermal drug delivery patch and theskin of a patient with said second heating element to provide relieffrom breakthrough pain.
 46. The method of claim 43, further comprisingthe steps of heating said dermal drug delivery patch and the skin of apatient with said second heating element to provide relief frombreakthrough cravings.
 47. The method of claim 43, further comprisingthe steps of heating said dermal drug delivery patch and the skin of apatient with said second heating element to provide relief frombreakthrough effects.
 48. The method of claim 43, further comprising thesteps of heating said dermal drug delivery patch and the skin of apatient with said second heating element to provide deeper drugpenetration .
 49. The method of claim 43, further comprising the stepsof heating said dermal drug delivery patch and the skin of a patientwith said second heating element to provide drug serum concentrationlevels that mimic a patient's circadian period.
 50. A method fordelivering a drug transdermally comprising the steps of: placing adermal drug delivery patch upon a patient's skin at an administrationsite; securing a cooling element compartment to said dermal drugdelivery patch; and disposing a freely transferrable cooling elementwithin the cooling element compartment.
 51. A method for delivering adrug transdermally comprising the steps of: placing a dermal drugdelivery patch upon a patient's skin at an administration site; securingan iontophoresis device compartment to said dermal drug delivery patch;and disposing an iontophoresis device within the heating elementcompartment.
 52. A method for transdermally delivering a drug comprisingthe steps of: securing a heating element structure on a patient's skin,said heating element structure comprising a heating element disposedabove the patient's skin and defining a drug patch compartment; anddisposing a dermal drug patch within said drug patch compartment, saiddrug patch being proximate to and capable of being heated by saidheating element, and said drug patch being freely transferrable into andout of the drug patch compartment.